Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

How to approach jaundice in the MRCP PACES exam.

For every medical trainee, the Membership of the Royal College of Physicians' Practical Assessment of Clinical Examination Skills (PACES) exam is one of the most difficult exams they must face in their career. It is designed to assess the clinical knowledge and skills of the trainee doctors who are entering higher specialist training. It sets rigorous standards to ensure the competence of the candidates across a range of skills. This article discusses a systematic approach to a patient with jaundice, which is a commonly encountered station in the exam, so that candidates will become more familiar with common causes and how to differentiate between these, as well as important bedside examination skills.

Quantitative examination of early diabetes by light-emitting diodes light-induced pupillary light reflex.

This study investigated the abnormal pupillary light reflex in patients with early diabetes mellitus (DM) without retinopathy by using a custom-made noninvasive portable pupilometer. The pupilometer recorded and analyzed the pupillary light reflex. Two light intensities, 0.2 cd and 1.2 cd, and four wavelengths of stimulus light-white (400 nm-800 nm), red (640 ± 5 nm), green (534 ± 5 nm), and blue (470 ± 5 nm)-were used to stimulate the pupil for 10 ms. The pupillary response was recorded for 15 s. A total of 40 healthy people and 40 people with DM without retinopathy participated in the experiment at the National Taiwan University Hospital. The mean and standard deviation of DM duration were 4.5 years and 3.9 years. Of the 16 indices, the duration that pupil restores from its minimum size to half of its resting size (DRP), maximum pupil restoration velocity (MRV), and average restoration velocity (ARV) exhibited the most significant differences between the healthy people and those with DM. Compared with healthy participants, DRP was 16.33% higher, and MRV and ARV were 17.45% and 4.58% lower, respectively, in those with DM. This might be attributable to the sympathetic nervous system (SNS) controlling the dilator muscle during the dark-adapted period and relaxing the pupil; the SNS had few degenerated nerve endings in people with DM. The three aforementioned indices might be used to evaluate the severity of autonomic neuropathy in early DM.

[Comparative characteristics of enzymatic hydrolysis methods for isolating toxic substances from blood and hair]. / Sravnitel'naya kharakteristika metodik fermentativnogo gidroliza dlya izolirovaniya toksichnykh veshchestv iz tsel'noi krovi i volos.

The aim of study was to develop methods for the hydrolysis with hyaluronidases for the isolation of drugs (phenobarbital, diphenhydramine hydrochloride and phenibut) from biological objects (blood, hair) and to compare their effectivenes with previously developed methods of enzymatic hydrolysis. The studies were carried out using model «blood - model drug substance (MDS)¼, a natural and artificially colored wool (hair) of laboratory animals - guinea pigs of white, red and black natural colors, which were daily given a solution of MDS and then were subjected to cosmetic effects - coloring. The isolation of MDS from the model complex «blood - MDS¼ and from wool was carried out using the developed methods of hydrolysis with proteolytic enzymes (papain, chymopsin and chymotrypsin) and hyaluronidase. Phenobarbital and diphenhydramine from hydrolysates were extracted by liquid-liquid extraction method, phenibut - by direct freezing extraction with acetonitrile. The analysis of the extracts was carried out by gas chromatography with mass selective detection. The results showed that the developed methods of enzymatic hydrolysis can be recommended for isolating substances of various properties (acidic, amphoteric and alkaline) from blood, natural and artificially colored wool (hair).

[The development of the method for enzymatic hydrolysis for the extraction of toxic substances from the hair samples]. / Razrabotka metodiki fermentativnogo gidroliza dlia izolirovaniia toksichnykh veshchestv iz obraztsov volos.

The objective of the present study was to develop and validate the method for the extraction of toxic substances from the hair samples as exemplified by enzymatic hydrolysis of barbituric acid derivatives. The experiments were carried out with the use of laboratory animals (white female rats and albino guinea pigs) that had been daily given a phenobarbital solution per os during 4 months preceding the study. The hairs obtained from the experimental animals were subjected to acid hydrolysis with a 6 mole hydrochloric acid and enzymatic hydrolysis with the use of chymopsin, trypsin, chymotrypsin, and papain solutions. The analysis of the extracted materials was performed by means of gas chromatography with mass-selective detection. The application of the proposed method for enzymatic hydrolysis produced the better results than acid hydrolysis. This technique was validated. The results of the study made possible the comparative characteristic of the effectiveness of acid and enzymatic hydrolysis.

Nephrolithiasis among male patients with newly diagnosed gout.

INTRODUCTION: An elevated serum urate level is recognised as a cause of gouty arthritis and uric acid stone. The level of serum uric acid that accelerates kidney stone formation, however, has not yet been clarified. This study aimed to find out if a high serum urate level is associated with nephrolithiasis. METHODS: Patients were recruited from the rheumatology clinic of Taipei City Hospital (Renai and Zhongxing branches) in Taiwan from March 2015 to February 2016. A total of 120 Chinese male patients with newly diagnosed gout and serum urate concentration of >7 mg/dL and no history of kidney stones were divided into two groups according to their serum urate level: <10 mg/dL (group 1, n=80) and ≥10 mg/dL (group 2, n=40). The mean body mass index, blood urea nitrogen level, creatinine level, urinary pH, and kidney ultrasonography were compared between the two groups. RESULTS: There were no significant differences in blood urea nitrogen or creatinine level between the two groups. The urine pH in both groups was similar and not statistically significant. Kidney stone formation was detected via ultrasonography in 6.3% (5/80) and 82.5% (33/40) of patients in groups 1 and 2, respectively (P<0.05). CONCLUSION: A serum urate level of ≥10 mg/dL may precipitate nephrolithiasis. Further studies are warranted to substantiate the relationship between serum urate level and kidney stone formation.

Zygotic Genome Activation Revisited: Looking Through the Expression and Function of Zscan4.

Zygotic genome activation (ZGA, a.k.a. zygotic gene activation) is a critical event in development, when the paternally derived genome and maternally derived genome begin to be activated and transcribed after fertilization. Major ZGA occurs at the two-cell stage in mice and the four- to eight-cell stage in human preimplantation embryos. It has been thought that ZGA exists to provide RNAs and proteins supporting embryonic development after supplies stored in oocytes are used up; however, this paradigm does not seem to explain recent findings. For example, many ZGA genes-once activated-are quickly turned off, and thus ZGA forms a transient wave of transcriptional activation. In addition, ZGA genes are not evolutionarily conserved. In this review, we address these issues by focusing on Zscan4 (zinc finger and SCAN domain-containing 4), which was identified for its specific expression in preimplantation embryos during ZGA. Detailed molecular analyses of Zscan4 expression and function have revealed common features of Zscan4-associated events (Z4 events) in mouse embryonic stem cells and ZGA in preimplantation embryos. One feature is a rapid derepression and rerepression of constitutive heterochromatin, which includes pericentromeric major satellites and telomeres, and facultative heterochromatin, which includes retrotransposons and Z4 event-associated genes. We propose that the Z4 event superimposed on ZGA plays a critical role in the maintenance of genome and chromosome integrity in preimplantation embryos by promoting correction of DNA damage and chromosome abnormalities.

NITRIC OXIDE SYNTHASE ACTIVITY AND ITS CONCENTRATION IN THE TISSUES OF HUMAN THYROID CARCINOMAS.

The study of the activity of the constitutive form of nitric oxide synthase (cNOS) revealed that in the papillary thyroid carcinomas it corresponded to that detected in unchanged extratumoral tissue, while the enzyme activity in follicular carcinoma was half lesser. At the same time, the activity of inducible nitric oxide synthase (іNOS) was higher in the papillary and follicular carcinomas. Such changes in the enzyme activity were associated with an increase in its level in papillary carcinomas, and with minor changes in follicular carcinomas. In medullary carcinomas the parameters under study corresponded to those in unchanged tissue, and in the papillary carcinoma metastases without changes in enzyme activity of nitric oxide formation, the level of the latter was much higher. Elevated levels of nitric oxide and іNOS activity in papillary thyroid carcinomas did not depend significantly on the aggression characteristics of the latter, being however absent in tumors of T4 category on a background of reduced cNOS activity and less expressed in tumors surrounded by the tissue in the presence of a chronic thyroiditis. Furthermore, in the papillary carcinomas of papillary or follicular structure nitric oxide level did not differ from the normal range, being slightly higher in tumors of solid or heterogeneous structure with presence of solid areas, whereas in carcinomas of papillary-follicular structure it was twice, and in tissue of solidinsular structure three times higher. іNOS hyperactivity was observed in the carcinomas of different structure, except for tumors of solid structure, in the tumor of which enzyme activity was within the normal range, and in tumor of solid-insular structure where it was significantly higher (as well as cNOS activity) compared with tumors of other structure. Nitric oxide generating system is involved in the transformation of thyroid cells and progression of tumor growth, including through apoptosis regulation, as shown by the results of an analysis of data obtained both in the present study and previously. The nature of such involvement in papillary thyroid carcinomas with different histological structure is different. Key words: nitric oxide; constitutive and inducible nitric oxide synthase; thyroid carcinoma; apoptosis.

Spinal antinociceptive effects of the novel NOP receptor agonist PWT2-nociceptin/orphanin FQ in mice and monkeys.

BACKGROUND AND PURPOSE: Using an innovative chemical approach, peptide welding technology (PWT), a tetrabranched derivative of nociceptin/orphanin FQ (N/OFQ) has been generated and pharmacologically characterized. Both in vitro and in vivo PWT2-N/OFQ displayed the same pharmacological profile to the natural ligand. It was more potent and produced longer-lasting effects. The aim of the present study was to investigate the spinal effects of PWT2-N/OFQ in nociceptive and neuropathic pain models in mice and non-human primates. EXPERIMENTAL APPROACH: Tail withdrawal assay in mice and monkeys was used as a nociceptive pain model and mechanical threshold in mice subjected to chronic constriction injury was used as a neuropathic pain model. The antinociceptive effects of spinally administered N/OFQ and PWT2-N/OFQ were assessed in these models. KEY RESULTS: PWT2-N/OFQ mimicked the spinal antinociceptive effects of N/OFQ both in nociceptive and neuropathic pain models in mice as well as in non-human primates displaying 40-fold higher potency and a markedly prolonged duration of action. The effects of N/OFQ and PWT2-N/OFQ were sensitive to the N/OFQ receptor (NOP) antagonist SB-612111, but not to opioid receptor antagonists. CONCLUSIONS AND IMPLICATIONS: The present study has demonstrated that PWT2-N/OFQ mimicked the antinociceptive effects of the natural peptide in rodents and non-human primates acting as a potent and longer-lasting NOP-selective agonist. More generally, PWT derivatives of biologically active peptides can be viewed as innovative pharmacological tools for investigating those conditions and states in which selective and prolonged receptor stimulation promotes beneficial effects.

Supraspinal actions of nociceptin/orphanin FQ, morphine and substance P in regulating pain and itch in non-human primates.

BACKGROUND AND PURPOSE: Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects of centrally administered ligands on regulating pain and itch in non-human primates. In particular, nociceptive thresholds affected by intracisternal N/OFQ were compared with those of morphine and substance P, known to provide analgesia and mediate hyperalgesia, respectively, in humans. EXPERIMENTAL APPROACH: Intrathecal catheters were installed to allow intracisternal and lumbar intrathecal administration in awake and unanaesthetized rhesus monkeys. Nociceptive responses were measured using the warm water tail-withdrawal assay. Itch scratching responses were scored from videotapes recording behavioural activities of monkeys in their home cages. Antagonist studies were conducted to validate the receptor mechanisms underlying intracisternally elicited behavioural responses. KEY RESULTS: Intracisternal morphine (100 nmol) elicited more head scratches than those after intrathecal morphine. Distinct dermatomal scratching locations between the two routes suggest a corresponding activation of supraspinal and spinal µ receptors. Unlike intracisternal substance P, which induced hyperalgesia, intracisternal N/OFQ (100 nmol) produced antinociceptive effects mediated by NOP receptors. Neither peptide increased scratching responses. CONCLUSIONS AND IMPLICATIONS: Taken together, these results demonstrated differential actions of ligands in the primate supraspinal region in regulating pain and itch. This study not only improves scientific understanding of the N/OFQ-NOP receptor system in pain processing but also supports the therapeutic potential of NOP-related ligands as analgesics.

Comparison of fine-needle aspiration and core needle biopsy under ultrasonographic guidance for detecting malignancy and for the tissue-specific diagnosis of salivary gland tumors.

BACKGROUND AND PURPOSE: Diagnostic test accuracy studies for ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy have shown inconclusive results due to their heterogenous study designs. Our aim was to compare the diagnostic accuracy of ultrasonography-guided fine-needle aspiration versus ultrasonography-guided core needle biopsy for detecting malignant tumors of the salivary gland and for the tissue-specific diagnosis of salivary gland tumors in a single tertiary hospital. MATERIALS AND METHODS: This retrospective study was approved by our institutional review board and informed consent was waived. Four hundred twelve patients who underwent ultrasonography-guided fine-needle aspiration (n = 155) or ultrasonography-guided core needle biopsy (n = 257) with subsequent surgical confirmation or clinical follow-up were enrolled. We compared the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy regarding malignant salivary gland tumors and the correct tissue-specific diagnosis of benign and malignant tumors. We also tested the difference between these procedures according to the operator's experience and lesion characteristics. RESULTS: The inconclusive rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 19% and 4%, respectively (P < .001). The overall accuracy of ultrasonography-guided core needle biopsy for diagnosing malignant tumors was significantly higher than that of ultrasonography-guided fine-needle aspiration (P = .024). The correct tissue-specific diagnosis rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 95% versus 97% for benign tumors (P = .648) and 67% versus 80% for malignant tumors (P = .310). Trainees showed significantly lower accuracy with ultrasonography-guided fine-needle aspiration than with ultrasonography-guided core needle biopsy for diagnosing malignant tumors (P = .021). There was no difference between the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy according to the internal composition of the lesions. There were no complications requiring intervention or hospitalization in our patients. CONCLUSIONS: Ultrasonography-guided core needle biopsy is superior to ultrasonography-guided fine-needle aspiration in detecting and characterizing malignant tumors of the salivary gland and could emerge as the diagnostic method of choice for patients presenting with a salivary gland mass.

QTL analysis of body weight and carcass body length traits in an F2 intercross between Landrace and Korean native pigs.

Growth traits, such as body weight and carcass body length, directly affect productivity and economic efficiency in the livestock industry. We performed a genome-wide linkage analysis to detect the quantitative trait loci (QTL) that affect body weight, growth curve parameters and carcass body length in an F2 intercross between Landrace and Korean native pigs. Eight phenotypes related to growth were measured in approximately 1000 F2 progeny. All experimental animals were subjected to genotypic analysis using 173 microsatellite markers located throughout the pig genome. The least squares regression approach was used to conduct the QTL analysis. For body weight traits, we mapped 16 genome-wide significant QTL on SSC1, 3, 5, 6, 8, 9 and 12 as well as 22 suggestive QTL on SSC2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 17. On SSC12, we identified a major QTL affecting body weight at 140 days of age that accounted for 4.3% of the phenotypic variance, which was the highest test statistic (F-ratio = 45.6 under the additive model, nominal P = 2.4 × 10(-11) ) observed in this study. We also showed that there were significant QTL on SSC2, 5, 7, 8, 9 and 12 affecting carcass body length and growth curve parameters. Interestingly, the QTL on SSC2, 3, 5, 6, 8, 9, 10, 12 and 17 influencing the growth-related traits showed an obvious trend for co-localization. In conclusion, the identified QTL may play an important role in investigating the genetic structure underlying the phenotypic variation of growth in pigs.

Increased expression of TRPC4 channels associated with erectile dysfunction in diabetes.

In recent reports, an association between altered TRPC channel function and the development of various diabetic complications has drawn the attention of many investigators. The aim of this study was to investigate the expression of TRPC4 channels of corpus smooth muscle (CSM) cells in diabetes, and to evaluate the association between erectile dysfunction (ED) and altered TRPC4 channel function. The expression of TRPC4 in the penile tissue of human, normal and diabetic rat was investigated using RT-PCR, western blotting and immunohistochemistry (IHC). In vivo gene transfer of dominant negative (DN) TRPC4 into the CSM of rat was conducted. In vivo pelvic nerve stimulation was performed to measure erectile function. Expression of TRPC1, TRPC3, TRPC4 and TRPC6 in human and rat CSM tissues was confirmed by RT-PCR, western blot and IHC. In the diabetic rat, the expression levels of mRNA and protein of the TRPC4, and TRPC6 were significantly increased compared to control rats (p < 0.05). The change in TRPC4 expression in the diabetic rats was higher than those of the other TRPC subunits (p < 0.05). The IHC showed that only TRPC4 expression had a higher intensity in the diabetes compared to normal rats (p < 0.05). Gene transfection with TRPC4(DN) into the diabetic rats restored erectile function to levels similar to that of normal controls. Gene expression of TRPC4(DN) in CSM tissue was confirmed by RT-PCR 2 weeks after transfection. This study demonstrated that TRPC4 channel expression increased in the penile CSM cells of diabetic rats. The down-regulation of TRPC4 with DN form restored erectile function in the diabetic rats. The alteration of TRPC4 channel is one of pathophysiology of ED and could be a target for drug development for ED.

[Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period].

Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug.

Functional plasticity of the N/OFQ-NOP receptor system determines analgesic properties of NOP receptor agonists.

Despite high sequence similarity between NOP (nociceptin/orphanin FQ opioid peptide) and opioid receptors, marked differences in endogenous ligand selectivity, signal transduction, phosphorylation, desensitization, internalization and trafficking have been identified; underscoring the evolutionary difference between NOP and opioid receptors. Activation of NOP receptors affects nociceptive transmission in a site-specific manner, with antinociceptive effects prevailing after peripheral and spinal activation, and pronociceptive effects after supraspinal activation in rodents. The net effect of systemically administered NOP receptor agonists on nociception is proposed to depend on the relative contribution of peripheral, spinal and supraspinal activation, and this may depend on experimental conditions. Functional expression and regulation of NOP receptors at peripheral and central sites of the nociceptive pathway exhibits a high degree of plasticity under conditions of neuropathic and inflammatory pain. In rodents, systemically administered NOP receptor agonists exerted antihypersensitive effects in models of neuropathic and inflammatory pain. However, they were largely ineffective in acute pain while concomitantly evoking severe motor side effects. In contrast, systemic administration of NOP receptor agonists to non-human primates (NHPs) exerted potent and efficacious antinociception in the absence of motor and sedative side effects. The reason for this species difference with respect to antinociceptive efficacy and tolerability is not clear. Moreover, co-activation of NOP and µ-opioid peptide (MOP) receptors synergistically produced antinociception in NHPs. Hence, both selective NOP receptor as well as NOP/MOP receptor agonists may hold potential for clinical use as analgesics effective in conditions of acute and chronic pain.

Superconducting properties of hole doped Ba(0.6)Li(0.4)Fe2As2 single crystal.

We report the emergence of superconductivity in Li doped Ba-122 single crystals grown by the Bridgman method. The superconducting transition temperature Tc,onset is around 19 K. The specific heat capacity C/T shows a weak anomaly near Tc. The value of ΔC/γnTc is smaller than the value predicted in BCS theory indicating a multigap nature of the sample. The magnetic measurements show that the lower critical field Hc1(T) exhibits a linear temperature dependence, with a pronounced change of the Hc1(T) curvature around 0.4Tc and Hc1(0) ≈ 430 Oe in the Ba0.6Li0.4Fe2As2 single crystal. Furthermore, temperature dependence of the penetration depth λ(T) follows a power law (~T(n)) below 0.4Tc which predicts possible S±-wave pairing in a Ba0.6Li0.4Fe2As2 superconductor. Over a wide range of temperatures, the Jc(H) exhibits a relation J(c)[proportionality] H(-α) with α = 0.5 ~ 0.6 for H || c and H || ab which indicates random defects in the sample. We found that the temperature dependence of the critical current density Jc(T) can be fitted well with the δl-type pinning model, whose origin is attributed to spatial variations of charge carrier mean free path l. We suggest that the large mismatch in the ionic radius of Ba and Li can affect the irreversible magnetic properties of the Ba0.6Li0.4Fe2As2 single crystal without any structural transition.

Gracilaria bursa-pastoris (Gmelin) Silva extract attenuates ultraviolet B radiation-induced oxidative stress in human keratinocytes.

The purpose of this study was to assess the protective effects of an ethanol extract derived from the red alga Gracilaria bursa-pastoris (Gmelin) Silva (GBE) on ultraviolet B (UVB)-irradiated human HaCaT keratinocytes. GBE exhibited scavenging activity against intracellular reactive oxygen species that were induced by either hydrogen peroxide or UVB radiation. In addition, both the superoxide anion and the hydroxyl radical were scavenged by GBE in cell-free systems. GBE absorbed light in the UVB range (280-320 nm) of the electromagnetic spectrum and lessened the extent of UVB-induced oxidative damage to cellular lipids, proteins, and DNA. Finally, GBE-treated keratinocytes showed a reduction in UVB-induced apoptosis, as exemplified by fewer apoptotic bodies. These results suggest that GBE exerts cytoprotective actions against UVB-stimulated oxidative stress by scavenging ROS and absorbing UVB rays, thereby attenuating injury to cellular constituents and preventing cell death.